Dendritic Cells Preferentially Transfer CXCR4 using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans

@article{citeulike:2875087, abstract = {Human immunodeficiency virus type-1 (HIV-1) preferentially utilizes the CCR5 coreceptor for target cell entry in the acute phase of infection, whilst later in disease progression the virus switches to the CXCR4-coreceptor in approximately 50\% of patients. In response to HIV-1 the adaptive immune response is triggered and antibody (Ab) production is elicited to block HIV-1 entry. We recently identified that dendritic cells (DCs) can efficiently capture Ab-neutralized HIV-1, restore infectivity, and transmit infectious virus to target cells. Here we tested the effect of Abs on trans-transmission of CCR5 or CXCR4 HIV-1 variants. We observed that transmission of HIV-1 by immature as well as mature DCs was significantly higher for CXCR4 than CCR5-tropic viral strains. Additionally, neutralizing Abs directed against either the gp41 or gp120 region of the envelope such as 2F5, 4E10, and V3-directed Abs inhibited transmission of CCR5 tropic HIV-1, whereas Ab-treated CXCR4-tropic virus demonstrated unaltered or increased transmission. To further study the effects of coreceptor usage we tested molecularly cloned HIV-1 variants with modifications in the envelope that were based on longitudinal gp120 V1 and V3 sequences from a patient progressing to AIDS. We observed that DCs preferentially facilitated infection of CD4+ T lymphocytes of viral strains with an envelope phenotype found late in disease. Taken together, our results illustrate that DCs transmit CXCR4-tropic HIV-1 much more efficiently than CCR5 strains; we hypothesize that this discrimination could contribute to the in vivo coreceptor switch after seroconversion and could be responsible for the increase in viral load. 10.1128/JVI.00245-08}, author = {van Montfort, Thijs and Thomas, Adri A. and Pollakis, Georgios and Paxton, William A. }, citeulike-article-id = {2875087}, doi = {http://dx.doi.org/10.1128/JVI.00245-08}, journal = {J. Virol.}, keywords = {dendritic, entry, hiv}, month = {June}, pages = {JVI.00245-08+}, posted-at = {2008-08-18 21:54:52}, priority = {2}, title = {Dendritic Cells Preferentially Transfer CXCR4 using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans}, url = {http://dx.doi.org/10.1128/JVI.00245-08}, year = {2008} }

TY - JOUR ID - citeulike:2875087 L3 - citeulike-article-id:2875087 N2 - Human immunodeficiency virus type-1 (HIV-1) preferentially utilizes the CCR5 coreceptor for target cell entry in the acute phase of infection, whilst later in disease progression the virus switches to the CXCR4-coreceptor in approximately 50% of patients. In response to HIV-1 the adaptive immune response is triggered and antibody (Ab) production is elicited to block HIV-1 entry. We recently identified that dendritic cells (DCs) can efficiently capture Ab-neutralized HIV-1, restore infectivity, and transmit infectious virus to target cells. Here we tested the effect of Abs on trans-transmission of CCR5 or CXCR4 HIV-1 variants. We observed that transmission of HIV-1 by immature as well as mature DCs was significantly higher for CXCR4 than CCR5-tropic viral strains. Additionally, neutralizing Abs directed against either the gp41 or gp120 region of the envelope such as 2F5, 4E10, and V3-directed Abs inhibited transmission of CCR5 tropic HIV-1, whereas Ab-treated CXCR4-tropic virus demonstrated unaltered or increased transmission. To further study the effects of coreceptor usage we tested molecularly cloned HIV-1 variants with modifications in the envelope that were based on longitudinal gp120 V1 and V3 sequences from a patient progressing to AIDS. We observed that DCs preferentially facilitated infection of CD4+ T lymphocytes of viral strains with an envelope phenotype found late in disease. Taken together, our results illustrate that DCs transmit CXCR4-tropic HIV-1 much more efficiently than CCR5 strains; we hypothesize that this discrimination could contribute to the in vivo coreceptor switch after seroconversion and could be responsible for the increase in viral load. 10.1128/JVI.00245-08 JF - J. Virol. TI - Dendritic Cells Preferentially Transfer CXCR4 using Human Immunodeficiency Virus Type 1 Variants to CD4+ T Lymphocytes in trans SP - JVI.00245-08 KW - dendritic KW - entry KW - hiv AU - van Montfort, Thijs AU - Thomas, Adri AU - Pollakis, Georgios AU - Paxton, William PY - 2008/06/04/ UR - http://dx.doi.org/10.1128/JVI.00245-08 ER -